Scientific background. Dysregulated systemic inflammation is a key pathogenetic mechanism for morbidity and mortality in ALI/ARDS, and is associated with tissue insensitivity and/or resistance to inappropriately elevated endogenous glucocorticoids. In one study, prolonged methylprednisolone treatment of ARDS patients resulted in rapid and sustained reduction in circulating and pulmonary levels of pro-inflammatory cytokines, chemokines, and procollagen.

Preliminary work. Five randomized trials (N = 518) investigating prolonged glucocorticoid treatment in acute lung injury/ARDS reported a significant physiological improvement and a sizable reduction in duration of mechanical ventilation and ICU length of stay. Insufficient data is available on the effects of low dose prolonged methylprednisolone treatment initiated in early ALI/ARDS on mortality.

Hypothesis. We hypothesized that the anti-inflammatory activity associated with prolonged methylprednisolone administration improves pulmonary and extra-pulmonary organ dysfunction in early ALI/ARDS and reduces mortality.

Objective. To investigate the effects of prolonged low-dose methylprednisolone infusion on mortality and morbidity in early ALI/ARDS.

End-points. The primary end-point of trial is 28 days all cause mortality; the secondary end-points are (a) ventilator-free days at 28 days following study entry, (b) organ failure-free days at 28 days following study entry, and (c) duration of ICU stay.

Further study details as provided by Catholic University of the Sacred Heart:

Primary Outcome Measures:

The primary aim is to determine if low-dose methylprednisolone infusion, compared to placebo, will reduce all cause 28-day mortality, defined as the proportion of patients alive in each group on study day 28 at midnight. [ Time Frame: one year ]

*Five days after the patient is able to ingest medications, methylprednisolone is given per os in one single daily equivalent dose.

†If between days 1 to 14 the patient is extubated, he is advanced to day 15 of drug therapy and tapered according to schedule.

‡ When leaving ICU, if the patient is still not tolerating p.o. intake for at least five days, he should receive the specified dosage as IV push every 6 hours until tolerating oral ingestion

Placebo Comparator: 2

Other: Normal saline intravenously and vitamin B1 per os

Patients in this group will receive sterile normal saline in an amount that would equal the total diluted dose of study drug (ie. if initial loading dose equals a total of 25 cc [prednisolone + diluting fluid], then the patient will receive 25 cc of sterile normal saline). Tapering doses will be equivalent to that of the study arm. Five days after the patient is able to ingest medications, placebo is administered per os in one single daily equivalent dose. The placebo will be a Vitamin B1 (thiamine) 50-mg tablet. We will now designate each placebo tab as a 16-mg equivalent to each tablet of active drug. These tablets are scored and half tabs can be given if needed. Therefore if a patient is receiving 40 mg of study drug: 40/16 = 2.5 tabs x 50 mg = 125 mg actual dose of thiamine.

Patients enrolled in another experimental (interventional) protocol within the past 30 days, which might adversely impact on the results of this study as determined by the investigators

Pregnancy confirmed by urine or serum test

Weight is > 200% of ideal body weight

Non-ambulatory resident of long-term care facility

Primary care physician not committed to full, aggressive support of the patient at the time of randomization

Moribund patient (i.e., not expected to live more than 24 hr) or with recent (within 7 days or anytime during present hospitalization) cardiopulmonary arrest

Known or suspected irreversible cessation of all brain function

Presence of preexisting medical condition which is irreversible and expected to be fatal within 3 months

Immunosuppression including HIV+ status, history of bone marrow or solid organ transplantation, current malignancy, neutropenia, receiving cytotoxic therapy for any reason, and acute burn injury

Severe chronic liver disease (Child-Pugh Class C score > 10 points)

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00562835